When a posterior or posterior-lateral fusion of selected spinal facet joints is desired, the surgeon may seek to enhance the fusion of these joints by placing a gel compound comprising graft material (such as autograft bone chips) and platelet-rich plasma (“PRP”) alongside the spinal ridges adjacent to the facet joints. The autograft bone chips contain matrix molecules and living cells such as osteoblasts, and the platelets in the PRP contain additional growth factors which facilitate fusion.
Procedures have been developed for producing this gel. For example, in one conventional process for making the bone chip/platelet-containing gel, the bone chips are placed in a small petri dish, and a 10:1 volumetric mixture of PRP and thrombin (a coagulation agent) is sprayed onto the bone chips. The fibrinogen in the PRP reacts with the thrombin to form clot-producing fibrin, thereby forming a clotted gel. Although this conventional process has been adopted by some surgeons, it nonetheless suffers from some drawbacks. For example, since the desired gel is produced in a flat dish, and not a syringe, it has a shape which is not preferred for facet fusion. In addition, since the dish is typically fairly open, the gel is in a relatively unprotected place. The spraying technique may also produce an uneven gel, thereby increasing the likelihood of open spaces. In addition, since the gel must ultimately be transferred from the dish, there is a risk that the clots in the gel will break. This is undesirable because breakage raises the possibility that the gel will migrate from the intended treatment location.
One conventional process seeks to avoid this problem by producing the gel within a syringe. FIG. 13a discloses a five port manifold A for delivering the PRP and thrombin precursors directly into a single receiving syringe R. In this process, two input ports Pi are randomly chosen to respectively receive one delivery syringe containing the PRP and one delivery syringe containing thrombin. Valves V associated with the non-selected ports are closed, and the precursor fluids within the delivery syringes D1 and D2 are emptied into the selected input ports. The precursor fluids travel through tubes within the manifold interior M and enter the receiving syringe R through a randomly selected output port Po to produce a gelled log of bone graft material. The manifold is typically stabilized by detachable legs K and L, and its ports are colinear.
One problem with using the conventional manifold of FIG. 13a is that the random nature of port selection within the five port manifold can lead to undesirable clotting within the manifold. For example, in the system shown in FIG. 13b, the two input ports B and C are randomly chosen to respectively receive syringe D containing the PRP and syringe E containing thrombin. Valves F and G from the non-selected ports are closed, and the fluids within the delivery syringes D and E are emptied into the ports B and C. As these precursor fluids travel through tube H, each passes through tube section N, thereby providing conditions favorable to clotting in tube section N. These conditions could inhibit the free flow of precursor materials through the manifold.
In addition, since it is common to require production of multiple logs of clotted gel per surgical procedure, it is desirable for the manifold to be free of clots not only during production of gel for the initial syringe, but also during gel production for additional syringes as well. However, the conventional manifold is also susceptible to clotting during subsequent procedures. For example, suppose the ports are fortuitously selected in a manner which avoids the above-mentioned instantaneous clotting problem during production of the initial gel. Such a selection is shown in FIG. 13c. Ports C and Z in FIG. 13c are selected for respective delivery of the PRP and thrombin fluids from syringes E and D to the output port J to produce the first gel log. However, during the production of this gel, tube sections N and O respectively become contaminated with PRP and thrombin. If, for production of the second gelled log, ports Q and B are then selected for respective delivery of the PRP and thrombin fluids to output port J, then the PRP-contaminated tube section N and the thrombin-contaminated tube section P will respectively combine with the thrombin from port B and the PRP from port Q, thereby causing undesired clotting in both of tube sections N and O. These clots in the manifold inhibit the flow of PRP and thrombin in the subsequent procedures.
Moreover, even if the three active ports are deliberately selected such that the output port is always between the two input ports (e.g., the system of FIG. 13b is selected and used for all four gel production procedures), there remains a problem in that the PRP and thrombin necessarily meet within tube section S of the manifold, thereby causing clotting within the manifold.
Thus, there is a need for a manifold suitable for producing a gelled log of bone graft material and which minimizes intra-manifold clotting.
Another problem with the conventional manifold shown in FIG. 13 lies in its stability. Applying conventional levels of force to the manifold during fluid delivery may often cause the manifold to tilt, despite the presence of stabilizing legs K and L. Thus, there is a need for a more stable manifold.
Lastly, the tubes within the manifold used in the process of FIG. 13c are often relatively large. For example, there may be about 0.4 cc of tubing between input port Z and output port J. Since a typical delivery syringe will contain only about 1 cc of thrombin, a significant volume of thrombin precursor material may never reach the receiving syringe R. In this case, the 0.4 cc lost volume may represent at least 40% of the PRP. Moreover, if the thrombin delivery syringe is not completely filled or if a non-adjacent output port is selected, the lost volume percentage may be even higher. Likewise, in a typical syringe delivering about 5 cc PRP, the lost volume of PRP in this manifold may be about 8%.
U.S. Pat. No. 5,935,437 discloses an apparatus for filtering blood plasma from whole blood, comprising three syringes in fluid communication with each other via tubes in a manifold, and a membrane housed within the tubes for selectively removing platelets from the blood. Whitmore discloses pores in the membranes filters of 0.2 and 0.55 microns (μm), and states that the pore size may or may not exclude platelets, which typically have a diameter of no more than about 2–3 um.
U.S. Pat. Nos. 4,735,616; 4,978,336; and 5,368,563 each disclose an apparatus useful for producing and administering fibrin glue. Each apparatus includes two syringes, each syringe containing a single glue precursor and received on a first side of a manifold, and an outlet on the opposite side of the manifold adapted for spraying the glue or glue precursors onto a target site.
U.S. Pat. No. 5,116,315 (“Capozzi”) describes a syringe system comprising a pair of syringes for delivering biological fluids through a manifold having a pair of ports for the attachment of the syringes, and flanges for attachment of either a spray assembly 20 or a needle assembly 18. Neither assembly is designed for retaining the fluids delivered from the syringes, but rather for expelling the fluids through a spray opening. Consequently, the volume defined by the manifold tubing 50 and 52 appears to be much greater than the volume defined by the spray assembly mixing space 84. The volume of the mixing space 84 appears to be less than 1 cc.
Therefore, it is an object of the present invention to provide a apparatus for mixing and retaining biological fluids comprising a manifold which minimizes intra-manifold mixing of the fluids. In addition, when the fluids comprise gel precursors, there is a particular need for minimizing intra-manifold clotting.